Further characterization of quinpirole-elicited yawning as a model of dopamine D3 receptor activation in male and female monkeys.

The dopamine (DA) D3 receptor (D3R) has been associated with impulsivity, pathologic gambling, and drug addiction, making it a potential target for pharmacotherapy development. Positron emission tomography studies using the D3R-preferring radioligand [(11)C]PHNO ([(11)C](+)-propyl-hexahydro-naphtho-oxazin) have shown higher binding potentials in drug abusers compared with control subjects. Preclinical studies have examined D3R receptor activation using the DA agonist quinpirole and the unconditioned behavior of yawning. However, the relationship between quinpirole-elicited yawning and D3R receptor availability has not been determined. In Experiment 1, eight drug-naive male rhesus monkeys were scanned with [(11)C]PHNO, and the ability of quinpirole (0.01-0.3 mg/kg i.m.) to elicit yawning was examined. Significant positive (globus pallidus) and negative (caudate nucleus, putamen, ventral pallidum, and hippocampus) relationships between D3R receptor availability and quinpirole-induced yawns were noted. Experiment 2 replicated earlier findings that a history of cocaine self-administration (n = 11) did not affect quinpirole-induced yawning and extended this to examine monkeys (n = 3) with a history of methamphetamine (MA) self-administration and found that monkeys with experience self-administering MA showed greater potency and significantly higher quinpirole-elicited yawning compared with controls. Finally, quinpirole-elicited yawning was studied in drug-naive female monkeys (n = 6) and compared with drug-naive male monkeys (n = 8). Sex differences were noted, with quinpirole being more potent and eliciting significantly more yawns in males compared with females. Taken together these findings support the use of quinpirole-elicited yawning as a behavioral tool for examining D3R activation in monkeys and that both drug history and sex may influence individual sensitivity to the behavioral effects of D3R compounds.

Bringing revolution through quadcopter technology in the field of supplying medicine in the Himalayan regions of Uttarakhand: Case example of Pithoragarh.

BACKGROUND: Quadcopters are used in various forms in the civil arena, from crop insurance to agricultural drones, as loudspeakers for announcing government guidelines, resilience tools in infrastructure monitoring, real-time vehicle detection, etc. However, the usage of quadcopters and hexacopters in supplying medical aid to inhospitable and far-flung terrains is being studied and researched in less detail throughout the globe. AIM: This paper focuses on the basics of quadcopter technology in supplying medicines and its advantages to the affected patients who get life-saving medicines from earlier inaccessible roads. The efficacy of quadcopters in terms of time, economy, and manpower in supplying essential and inescapable medical supplies is exponentially high, especially in the Pithoragarh Region of Uttarakhand State, where the villages are not connected to the roads. METHODS: The road structure of the hilly terrain of Uttarakhand, India, was studied in detail to know the state of people who do not get access to life-saving drugs due to the non-availability of roads near them. RESULTS: The result informs us that the quad/hexacopter if used in abundance can provide a glimmer of hope to people in remote places. CONCLUSION: The quadcopter can provide hope to the residents of the Pithoragarh district of Uttarakhand, India, located in far-flung places devoid of basic medical facilities.

Low dose mifepristone in medical management of uterine leiomyoma - an experience from a tertiary care hospital from north India.

BACKGROUND & OBJECTIVES: Uterine myoma is a common indication for hysterectomy in India. An effective medical treatment option may reduce hysterectomy associated morbidity. This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day. METHODS: In this randomized clinical trial, women with symptomatic myoma or myoma>5 cm were included. Uterine size >20 wk, fibroids >15 cm were excluded. Pictorial blood loss assessment chart (PBAC) score was used to assess menstrual-blood-loss and visual analog scale (VAS) for other symptoms. Haemogram, liver function test, ultrasound with doppler and endometrial histology was performed. Patients were randomized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months. Patients were followed at 1, 3 and 6 months. RESULTS: Seventy patients in group 1 and 73 in group 2 completed treatment. Mean PBAC score reduced from 253 to 19.8 and from 289.2 to 10.4 at 1 and 3 months in groups 1 and 2, respectively. At 3 months, 67 of 70 (95.7%) patients of group 1 and 66 of 73 (90.4%) of group 2 developed amenorrhoea which reverted after median 34 (range 4-85) days. Mean myoma volume decreased by 35.7 per cent (from 176.8 to 113.7 cm 3 ) and 22.5 per cent (from 147.6 to 114.4 cm 3 ) at 3 months in groups 1 and 2, respectively. Side effects seen were leg cramps in 7 of 70 (10%) and 5 of 73 (6.8%) and hot-flushes in 5 of 70 (7.1%) and 5 of 73 (6.8%) in groups 1 and 2, respectively. Repeat endometrial-histopathology did not reveal any complex hyperplasia or atypia in either group. INTERPRETATION & CONCLUSIONS: Mifepristone (10 and 25 mg) caused symptomatic relief with more than 90 per cent reduction in menstrual blood. Greater myoma size reduction occured with 25 mg dose. Amenorrhoea was developed in 90-95 per cent patients which was reversible. It can be a reasonable choice for management of uterine leiomyoma as it is administered orally, cost-effective and has mild side effects.

Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine.

Tobacco smoking is a chronic, relapsing disorder that constitutes one of the primary preventable causes of death in developed countries. Two of the popular hypotheses to explain the development and maintenance of strong nicotine dependence in cigarette smokers posit (i) a rapid brain nicotine accumulation during cigarette smoking and/or (ii) puff-associated spikes in brain nicotine concentration. To address these hypotheses, we investigated the dynamics of nicotine accumulation in the smoker's brain during actual cigarette smoking using PET with 3-s temporal resolution and (11)C-nicotine loaded into cigarettes. The results of the study, performed in 13 dependent smokers (DS) and 10 nondependent smokers (NDS), suggest that puff-associated spikes in the brain nicotine concentration do not occur during habitual cigarette smoking. Despite the presence of a puff-associated oscillation in the rate of nicotine accumulation, brain nicotine concentration gradually increases during cigarette smoking. The results further suggest that DS have a slower process of brain nicotine accumulation than NDS because they have slower nicotine washout from the lungs and that DS have a tendency to compensate for their slower rate of brain nicotine accumulation compared with NDS by inhaling a larger volume of smoke. For these reasons, smokers' dependence on cigarette smoking, or the resistance of NDS to becoming dependent, cannot be explained solely by a faster brain nicotine accumulation.

Internal jugular vein thrombosis: an uncommon presentation.

Internal jugular vein (IJV) thrombosis is a rare entity. It is usually secondary to various etiologies such as ovarian hyperstimulation, deep vein thrombosis of upper limbs, venous catheter, malignancy, trauma, infection, and neck surgery and hypercoagulable status. We report an unusual case of internal jugular vein thrombosis with cerebral sinus thrombosis, postpartum in a 22-year-old female patient who presented with a painful swelling on the left side of her neck. Diagnosis was established by color Doppler ultrasonography and magnetic resonance venography. Thorough evaluation of the patient revealed no etiological factor leading to thrombosis. Patient was treated with low-molecular-weight heparin.

Single visit approach for management of cervical intraepithelial neoplasia by visual inspection & loop electrosurgical excision procedure.

BACKGROUND & OBJECTIVES: Developing a feasible and sustainable model of cervical cancer screening in developing countries continues to be a challenge because of lack of facilities and awareness in the population and poor compliance with screening and treatment. This study was aimed to evaluate a single visit approach (SVA) for the management of cervical intraepithelial neoplasia (CIN) using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) along with loop electrosurgical excision procedure (LEEP) in women attending Gynaecology OPD in a tertiary care hospital in north India. METHODS: In this hospital-based study, 450 women receiving opportunistic screening by conventional Pap cytology were also screened by VIA and VILI. VIA/VILI positive cases underwent same-day colposcopy and biopsy of all lesions. If the modified Reid score was >3, the patient underwent LEEP at the same visit. RESULTS: Of the 450 women screened, 86 (19.1%) and 92 (20.5%) women were VIA and VILI positive, respectively. Detection rates of VIA, VILI and cytology findings at ASCUS threshold were 33.3, 35.5 and 24.4 per 1000, women, respectively to detect a lesion >CIN1. For detection of CIN2+ lesion, detection rates of VIA, VILI and cytology were 20, 22.2 and 22.2 per 1000 women, respectively. Sixteen patients with Reid score >3 underwent the "See-and-treat" protocol. The overtreatment rate was 12.5 per cent and the efficacy of LEEP was 81.3 per cent. There were no major complications. INTERPRETATION & CONCLUSIONS: The sensitivity of VIA/VILI was comparable to cytology. A single visit approach using visual screening methods at community level by trained paramedical personnel followed by a combination of ablative and excisional therapy can help to decrease the incidence of cervical neoplasia.

Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy.

Simlukafusp alfa (FAP-IL2v, RO6874281/RG7461) is an immunocytokine comprising an antibody against fibroblast activation protein α (FAP) and an IL-2 variant with a retained affinity for IL-2Rßγ > IL-2 Rßγ and abolished binding to IL-2 Rα. Here, we investigated the immunostimulatory properties of FAP-IL2v and its combination with programmed cell death protein 1 (PD-1) checkpoint inhibition, CD40 agonism, T cell bispecific and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. The binding and immunostimulatory properties of FAP-IL2v were investigated in vitro and compared with FAP-IL2wt. Tumor targeting was investigated in tumor-bearing mice and in a rhesus monkey. The ability of FAP-IL2v to potentiate the efficacy of different immunotherapies was investigated in different xenograft and syngeneic murine tumor models. FAP-IL2v bound IL-2 Rßγ and FAP with high affinity in vitro, inducing dose-dependent proliferation of natural killer (NK) cells and CD4+/CD8+ T cells while being significantly less potent than FAP-IL2wt in activating immunosuppressive regulatory T cells (Tregs). T cells activated by FAP-IL2v were less sensitive to Fas-mediated apoptosis than those activated by FAP-IL2wt. Imaging studies demonstrated improved tumor targeting of FAP-IL2v compared to FAP-IL2wt. Furthermore, FAP-IL2v significantly enhanced the in vitro and in vivo activity of therapeutic antibodies that mediate antibody-dependent or T cell-dependent cellular cytotoxicity (TDCC) and of programmed death-ligand 1 (PD-L1) checkpoint inhibition. The triple combination of FAP-IL2v with an anti-PD-L1 antibody and an agonistic CD40 antibody was most efficacious. These data indicate that FAP-IL2v is a potent immunocytokine that potentiates the efficacy of different T- and NK-cell-based cancer immunotherapies.

Geospatial analysis of HIV-Related social stigma: a study of tested females across mandals of Andhra Pradesh in India.

BACKGROUND: In Geographical Information Systems issues of scale are of an increasing interest in storing health data and using these in policy support. National and international policies on treating HIV (Human Immunodeficiency Virus) positive women in India are based on case counts at Voluntary Counseling and Testing Centers (VCTCs). In this study, carried out in the Indian state of Andhra Pradesh, these centers are located in subdistricts called mandals, serving for both registration and health facility policies. This study hypothesizes that people may move to a mandal different than their place of residence for being tested for reasons of stigma. Counts of a single mandal therefore may include cases from inside and outside a mandal. HIV counts were analyzed on the presence of outside cases and the most likely explanations for movement. Counts of women being tested on a practitioners' referral (REFs) and those directly walking-in at testing centers (DWs) were compared and with counts of pregnant women. RESULTS: At the mandal level incidence among REFs is on the average higher than among DWs. For both groups incidence is higher in the South-Eastern coastal zones, being an area with a dense highway network and active port business. A pattern on the incidence maps was statistically confirmed by a cluster analysis. A spatial regression analysis to explain the differences in incidence among pregnant women and REFs shows a negative relation with the number of facilities and a positive relation with the number of roads in a mandal. Differences in incidence among pregnant women and DWs are explained by the same variables, and by a negative relation with the number of neighboring mandals. Based on the assumption that pregnant women are tested in their home mandal, this provides a clear indication that women move for testing as well as clues for explanations why. CONCLUSIONS: The spatial analysis shows that women in India move towards a different mandal for getting tested on HIV. Given the scale of study and different types of movements involved, it is difficult to say where they move to and what the precise effect is on HIV registration. Better recording the addresses of tested women may help to relate HIV incidence to population present within a mandal. This in turn may lead to a better incidence count and therefore add to more reliable policy making, e.g. for locating or expanding health facilities.

Post-hysterectomy menstruation: a rare phenomenon.

Post-menopausal bleeding is a common problem with varied etiology in the age group between 50 and 60 years. It is more likely to be of some pathologic cause which needs to be ruled out. Bleeding in a patient after hysterectomy is even rarer with varied causes like atrophic vaginitis, cervical stump cancer, infiltrating ovarian tumors, estrogen secreting tumors in other parts of the body. Endometriosis of the vault sometimes can cause post-menopausal bleeding. Diverticulitis of the bowel may give rise to vaginal discharge due to fistula, but bleeding is rare. Bladder pathology may cause vaginal bleeding. Our case is a rare case of vault endometriosis and should always be kept as a differential diagnosis in patients with bleeding after hysterectomy.

Rapid Brain Nicotine Uptake from Electronic Cigarettes.

This study sought to determine brain nicotine kinetics from use of the increasingly popular electronic cigarette (E-cig). Methods: In 17 E-cig users (9 men and 8 women), brain uptake of nicotine after inhalation from E-cigs was directly assessed using 11C-nicotine PET. The brain nicotine kinetics were compared with those from smoking combustible cigarettes (C-cigs). Results: A single puff of E-cig vapor caused the nicotine concentration in the brain to rise quickly (mean time to reach 50% of maximum brain nicotine concentration, 27 s), with a peak amplitude 25% higher in women than men, resembling previous observations with C-cigs. Nonetheless, the accumulation from E-cigs (24%) was less than that from C-cigs (32%) in both men and women. Conclusion: E-cigs can deliver nicotine to the brain with a rapidity similar to that of C-cigs. Therefore, to the extent that rapid brain uptake promotes smoking reward, E-cigs might maintain a degree of nicotine dependence and also serve as a noncombustible substitute for cigarettes.

Visual interpretation, not SUV ratios, is the ideal method to interpret 18F-DOPA PET scans to aid in the cure of patients with focal congenital hyperinsulinism.

INTRODUCTION: Congenital hyperinsulinism is characterized by abnormal regulation of insulin secretion from the pancreas causing profound hypoketotic hypoglycemia and is the leading cause of persistent hypoglycemia in infants and children. The main objective of this study is to highlight the different mechanisms to interpret the 18F-DOPA PET scans and how this can influence outcomes. MATERIALS AND METHODS: After 18F-Fluoro-L-DOPA was injected intravenously into 50 subjects' arm at a dose of 2.96-5.92 MBq/kg, three to four single-bed position PET scans were acquired at 20, 30, 40 and 50-minute post injection. The radiologist interpreted the scans for focal and diffuse hyperinsulinism using a visual interpretation method, as well as determining the Standard Uptake Value ratios with varying cut-offs. RESULTS: Visual interpretation had the combination of the best sensitivity and positive prediction values. CONCLUSIONS: In patients with focal disease, SUV ratios are not as accurate in identifying the focal lesion as visual inspection, and cases of focal disease may be missed by those relying on SUV ratios, thereby denying the patients a chance of cure. We recommend treating patients with diazoxide-resistant hyperinsulinism in centers with dedicated multidisciplinary team comprising of at least a pediatric endocrinologist with a special interest in hyperinsulinism, a radiologist experienced in interpretation of 18F-Fluoro-L-DOPA PET/CT scans, a histopathologist with experience in frozen section analysis of the pancreas and a pancreatic surgeon experienced in partial pancreatectomies in patients with hyperinsulinism.

Design, synthesis, and preliminary in vitro and in vivo evaluation of N-(2-diethylaminoethyl)-4-[18F]fluorobenzamide ([18F]-DAFBA): a novel potential PET probe to image melanoma tumors.

In order to develop a PET radiopharmaceutical to image malignant melanoma, we synthesized N-(2-diethylaminoethyl)-4-[(18)F]fluorobenzamide ([(18)F]-DAFBA). In vitro studies show a high uptake of [(18)F]-DAFBA by the B16F1 melanoma cells. No significant binding was seen for DAFBA to the sigma-1 and sigma-2 receptors in vitro. The in vivo biodistribution studies performed in normal ICR mice showed a low uptake in the normal tissues followed by further elimination of radioactivity from these tissues with time. The biodistribution studies performed in C57 mice bearing the melanoma tumor xenograft showed a rapid uptake of radioactivity in the tumor that reached a plateau within 30 min postinjection. The F-18 uptake in the tumor was 7.00 +/- 2.76, 6.57 +/- 1.66, and 5.80 +/- 0.98%ID/g at 60, 120, and 180 min, respectively. A steady uptake of radioactivity in the tumor and low uptake in normal tissues resulted in high tumor to normal tissue ratios. For example, at 180 min postinjection, the tumor to tissue ratios were 14.90 +/- 6.47, 21.90 +/- 4.68, 32.91 +/- 6.11, 39.73 +/- 11.78, and 6.33 +/- 1.9, for the spleen, lungs, muscle, blood, and liver, respectively. The radioactivity rapidly cleared from the blood pool, and it decreased from 0.68 +/- 0.21%ID/g at 60 min to 0.13 +/- 0.03%ID/g at 180 min. The F-18 uptake in the bones at 60, 120, and 180 min was 0.91 +/- 0.27, 0.57 +/- 0.32, and 0.17 +/- 0.05%ID/g, respectively. This low uptake in the bones reflects its in vivo resistance toward defluorination. A low residual activity in normal tissues and a high tumor uptake signifies the superior imaging potential of this compound. Because of these positive traits, [(18)F]-DAFBA could help delineate the tumor and its metastases when used for imaging applications. Further in vivo studies are underway to assess the potential of [(18)F]-DAFBA as a promising PET imaging probe.

Enhanced cholinergic response in pancreata of nonhuman primates with impaired glucose tolerance shown on [18F]fluorobenzyltrozamicol positron emission tomography.

BACKGROUND: Islet cell adaptation to insulin resistance in type 2 diabetes mellitus may be due in part to increased stimulation of beta cells by the autonomic nervous system. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor correlates with cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[18F]fluorobenzyltrozamicol ([18F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. In this study, we utilize [18F]FBT PET to demonstrate pancreatic cholinergic activity before and after dextrose infusion in nonhuman primates with normal (NGT) and impaired (IGT) glucose tolerance. METHODS: Seven adult female vervet (Chlorocebus aethiops) monkeys were maintained on an atherogenic Western diet. They were divided into two groups: four with NGT and three with IGT. Each subject underwent [18F]FBT PET twice: first, a baseline PET under fasting conditions; and second, PET under fasting conditions but after intravenous infusion of dextrose solution. Quantitative analysis of pancreatic uptake at 60 min post-injection was performed. RESULTS: There was no difference in pancreatic uptake of [18F]FBT on baseline scans between the two groups. Pancreatic uptake of [18F]FBT increased in every subject after dextrose infusion (P = 0.03). On post-dextrose PET scans, pancreatic uptake of [18F]FBT was significantly higher in IGT subjects compared with NGT subjects (P = 0.03). The post-dextrose to pre-dextrose uptake ratios were higher in IGT subjects (P = 0.08). CONCLUSIONS: Acute increases in pancreatic cholinergic activity in vivo were detected in the pancreata of nonhuman primates with NGT and IGT after intravenous dextrose infusion on [18F]FBT PET. In subjects with IGT, this activity was significantly higher, suggesting increased autonomic nervous system stimulation of the pancreatic islets in insulin-resistant subjects.

Dual radiotracer analysis of cholinergic neuronal changes in prediabetic mouse pancreas.

BACKGROUND: Pancreatic neuronal changes associated with beta cell loss in type 1 diabetes mellitus are complex, involving, in part, parasympathetic mechanisms to compensate for preclinical hyperglycemia. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor has been shown to be a useful marker of cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[(18)F]fluorobenzyltrozamicol ([(18)F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. The compound 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), available in a tritiated form, binds to M3 muscarinic receptors on beta cells and is a potential target for assessing pancreatic beta cell mass. In this study, we investigate the feasibility of dual radiotracer analysis in identifying neurofunctional changes that may signify type 1 diabetes mellitus in its early preclinical state. METHODS: Ex vivo determinations of pancreatic uptake were performed in prediabetic nonobese diabetic mice and controls after intravenous injection of [(18)F]FBT or 4-[(3)H]DAMP. Beta cell loss in prediabetic mice was confirmed using immunohistochemical methods. RESULTS: [(18)F]FBT uptake was significantly higher in prediabetic pancreata than controls: 3.22 +/- 0.81 and 2.51 +/- 1.04, respectively (P < 0.03). 4-[(3)H]DAMP uptake was significantly lower in prediabetic pancreata than controls: 0.612 +/- 0.161 and 0.968 +/- 0.364, respectively (P = 0.01). CONCLUSIONS: These data suggest that a combination of radiotracer imaging agents that bind to neuronal elements intimately involved in insulin production may be an effective method of evaluating changes associated with early beta cell loss using PET.

Whole Body PET Imaging with a Norepinephrine Transporter Probe 4-[18F]Fluorobenzylguanidine: Biodistribution and Radiation Dosimetry.

PURPOSE: 4-[18F]Fluorobenzylguanidine ([18F]PFBG) is a positron emission tomography (PET) probe for non-invasive targeting of the norepinephrine transporter. The aim of this study was to assess uptake and distribution characteristics of this PET probe. PROCEDURES: Three cynomolgus monkeys were injected with 269 ± 51 MBq (7.3 ± 1.4 mCi) of [18F]PFBG and 21 whole body PET scans were acquired over 165 min. s around organs to generate time-activity curves. The absorbed doses to individual organs and the effective dose to the whole body were estimated. RESULTS: Favorable distribution of [18F]PFBG was noted with a fast wash-in and wash-out of radioactivity from several tissues. [18F]PFBG rapidly distributed in the heart, liver, kidneys, and adrenal glands. The uptake presented as %ID in the brain, lung, and spleen was 1.06 ± 0.45, 6.28 ± 0.33, and 1.39 ± 0.35 at 1 min and decreased to 0.29 ± 0.02, 1.78 ± 0.31, and 0.66 ± 0.22 by 112 min. In general, a two- to fourfold reduction was noted from peak radioactivity levels. Rapid uptake and significant retention of radioactivity was noted in the heart and the septal wall was distinctly visible by 20 min. Fast wash-in and washout kinetics for [18F]PFBG resulted in shorter residence times. The residence time for the liver, lungs, kidneys, and spleen were 28.01 ± 7.73 min, 2.97 ± 0.56 min, 6.04 ± 3.41 min, and 1.09 ± 0.33 min, respectively. The mean effective dose for the 70-kg male was 0.04 ± 0.00 mSv/MBq. The organs receiving the highest radiation dose in the 70-kg male model were the testes (0.11 ± 0.02 mGy/MBq), adrenals (0.08 ± 0.01 mGy/MBq), and urinary bladder wall (0.08 ± 0.01 mGy/MBq). CONCLUSIONS: [18F]PFBG shows a favorable biodistribution pattern. Rapid and persistent uptake was noted in innervated organs. Renal clearance was the major path for elimination of [18F]PFBG. The estimated radiation burden from [18F]PFBG was significantly lower than that from [124I]MIBG.

Effects of cocaine and MDMA self-administration on serotonin transporter availability in monkeys.

Although serotonin (5-HT) can interact with dopamine (DA) systems to modulate the subjective and reinforcing effects of psychostimulants such as cocaine and 3,4-methyldioxymethamphetamine (MDMA, ecstasy), the long-term effects of exposure to psychostimulants on brain 5-HT systems are not well characterized. The present study assessed 5-HT transporter (SERT) availability using positron emission tomography (PET) in rhesus monkeys with the SERT-specific radioligand [(11)C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB). SERT availability was assessed in regions of interest including the caudate nucleus, putamen, anterior cingulate cortex, and cerebellum. [(11)C]DASB distribution volume ratios (DVRs) were calculated using the cerebellum as the reference region. DVRs were calculated in control monkeys and in cocaine or MDMA self-administering monkeys approximately 24 h after the last self-administration (SA) session. SERT availability did not differ between monkeys with a history of MDMA SA and control monkeys in any region examined. In contrast, monkeys with a history of cocaine SA showed significantly higher levels of SERT availability in the caudate nucleus and putamen compared to control subjects. These results suggest that chronic SA of cocaine, but not MDMA, leads to alterations in serotonergic function in brain areas relevant to drug abuse. The higher level of SERT availability in cocaine-experienced monkeys may lead to a reduced inhibitory tone of 5-HT on the DA system, which may explain, in part, differences in the abuse liability between cocaine and MDMA.

A review of total laparoscopic hysterectomy using LigaSure uterine artery-sealing device: AIIMS experience.

STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of total laparoscopic hysterectomy (TLH) by using the Ligasure system for the sealing of uterine arteries. DESIGN: We conducted a retrospective review of cases who underwent TLH over 1.5 years. SETTINGS: This study was conducted in a tertiary care hospital setting, at the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (New Delhi, India). PATIENTS: A total of 110 patients of TLH done for uterine pathology [leiomyoma in 67 (60.9%), dysfunctional uterine bleeding in 34 (30.9%), and others in 9 (8.1%)]. INTERVENTIONS: Total laparoscopic hysterectomy, using the LigaSure system (Valleylab Inc., Boulder, CO), was done by the sealing of uterine arteries and Prashant Mangeshikar uterine manipulator for elevation of the uterus. RESULTS: The mean age of the patients was 43.1 +/- 0.602 years and mean body mass index was 25.19 +/- 0.39 kg/m(2). The mean operating time was 116.91 +/- 3.4 minutes, mean intraoperative blood loss was 173.09 +/- 11.64 mL, and the mean weight of the removed uterus was 224.14 +/- 17.62 g. Six patients were converted from a laparoscopic to an open procedure (large myoma in 4 and dense adhesion in 2) and 1 was converted to laparoscopically assisted vaginal hysterectomy (tear in vaginal cuff). One patient (0.9%) developed lung emphysema during the intraoperative period. Postoperative complications included paralytic ileus in 3 (2.7%), retention of urine in 2 (1.8%), and febrile morbidity in 12 (10.9%) patients. There were no bladder or bowel injuries. CONCLUSION: Laparoscopic hysterectomy by uterine artery sealing with LigaSure is a safe, efficient procedure with a low complication rate.

A remote controlled system for the preparation of 7 alpha-[18F]fluoro-17 alpha-methyl 5 alpha-dihydrotestosterone ([18F]FMDHT) using microwave.

For non-invasive imaging of the prostate cancer, we synthesized 7 alpha-fluoro-17 alpha-methyl 5 alpha-dihydrotestosterone ([(18)F]FMDHT) for androgen receptor mediated PET imaging. Preliminary in vitro and in vivo evaluations of this compound show promise. We designed and implemented a remote controlled system for reliable, efficient, and safe handling of radioactivity during the radiochemical synthesis of [(18)F]FMDHT. The key features of this report are the microwave assisted radiochemical synthesis, increased radiochemical yields, improved radiochemical purity, reduced overall synthesis time, and remote controlled automation of the entire synthesis. The overall synthesis using microwave reaction took 60-70 min and provided the desired product in 20-30% radiochemical yields with >99% radiochemical purity.

Retained percutaneous tube--a misery of illiteracy.

Percutaneous catheter drainage of liver abscesses is an established technique. Intracavitatory knotting of the tube is a rare and potentially preventable complication that can involve significant morbidity. However, because of the rarity of this complication, there remains a persistent lack of awareness in the clinical community. The risk of tube knotting can be reduced with proper technique and correct choice of tubes.

Post-sterilization regrets in Indian women.

BACKGROUND: Tubal ligation is the most common form of contraception in India. We conducted this study to assess the factors associated with post-sterilization regrets. AIMS: This study was designed to assess risk factors that are likely to cause regret following female sterilization in Indian women. SETTINGS AND DESIGN: Questionnaire-based study. MATERIALS AND METHODS: This was a questionnaire-based study to assess the level of satisfaction after tubal ligation in women attending family planning clinic at the hospital over a period of 1 year. Evaluation of data obtained through questionnaire from 236 women who had undergone tubal ligation was done. STATISTICAL ANALYSIS: Univariate analysis to determine crude odds ratio was carried out. Subsequently, multiple regression analysis was used to find the adjusted odds ratio (and 95% confidence intervals) for each variable. RESULTS: We found a strong co-relation between regrets and young age (less than 30 years), fewer number of children, few or no male children and lack of partner motivation prior to sterilization. Menstrual irregularities and dysmenorrhoea did not influence regret to a large extent. CONCLUSION: Fertility-related factors, namely, age at sterilization, family size, number of male offspring, timing of sterilization and non-involvement of partner in decision making played a greater role in post-sterilization regrets than menstrual factors (menstrual irregularities and dysmenorrhoea).